Podcasts about cytotoxic

CME credits: 0.25 Valid until: 16-04-2026 Claim your CME credit at https://reachmd.com/programs/cme/second-line-chemotherapy-options-in-metastatic-pdac/33136/ Pancreatic ductal adenocarcinoma, also known as PDAC, is a lethal disease that is usually diagnosed at an advanced stage with an extremely poor prognosis. Advancements in treatment regimens have improved survival rates, but early diagnosis is crucial for improving outcomes, and awareness of risk factors is vital for early diagnosis. Cytotoxic chemotherapy is the cornerstone of treatment for advanced or metastatic cases, although molecularly targeted therapies and immunotherapies may benefit select patients. Treatment selection depends on several factors, including patients' performance status and comorbidities, which should be considered alongside the efficacy and safety profiles of the different chemotherapy regimens. This two-part programme provides an overview of the different first- and second-line chemotherapy options. Complete both modules, answer pre- and post-test questions and start earning CME credits. This programme is also featured on the COR2ED website, here: Chemotherapy Strategies for Metastatic Pancreatic Ductal Adenocarcinoma

CME credits: 0.25 Valid until: 16-04-2026 Claim your CME credit at https://reachmd.com/programs/cme/first-line-chemotherapy-options-in-metastatic-pdac/33135/ Pancreatic ductal adenocarcinoma, also known as PDAC, is a lethal disease that is usually diagnosed at an advanced stage with an extremely poor prognosis. Advancements in treatment regimens have improved survival rates, but early diagnosis is crucial for improving outcomes, and awareness of risk factors is vital for early diagnosis. Cytotoxic chemotherapy is the cornerstone of treatment for advanced or metastatic cases, although molecularly targeted therapies and immunotherapies may benefit select patients. Treatment selection depends on several factors, including patients' performance status and comorbidities, which should be considered alongside the efficacy and safety profiles of the different chemotherapy regimens. This two-part programme provides an overview of the different first- and second-line chemotherapy options. Complete both modules, answer pre- and post-test questions and start earning CME credits. This programme is also featured on the COR2ED website, here: Chemotherapy Strategies for Metastatic Pancreatic Ductal Adenocarcinoma

CME credits: 0.25 Valid until: 13-01-2026 Claim your CME credit at https://reachmd.com/programs/cme/chemotherapy-strategies-for-metastatic-pdac/26435/ Pancreatic ductal adenocarcinoma, otherwise known as PDAC, is a lethal disease which is usually diagnosed at an advanced stage and has an extremely poor prognosis. Advancements in treatment regimens have improved survival rates, but early diagnosis is crucial for improving outcomes and awareness of risk factors is vital for early diagnosis. Cytotoxic chemotherapy is the cornerstone of treatment for advanced or metastatic cases, although molecularly targeted therapies and immunotherapies may benefit select patients. Treatment selection depends on several factors, including patients' performance status and co-morbidities and these should be considered alongside the efficacy and safety profiles of the different chemotherapy regimens. This 2-part microlearning provides an overview of the risk factors, diagnostic tools and treatment options available to date for different patient groups. Complete both modules, answer pre- and post-test questions and start earning CME credits. This programme is also featured on the COR2ED website, here: Metastatic pancreatic ductal adenocarcinoma (PDAC): from diagnosis to treatment

CME credits: 0.25 Valid until: 13-01-2026 Claim your CME credit at https://reachmd.com/programs/cme/diagnosis-and-management-of-metastatic-pdac/26434/ Pancreatic ductal adenocarcinoma, otherwise known as PDAC, is a lethal disease which is usually diagnosed at an advanced stage and has an extremely poor prognosis. Advancements in treatment regimens have improved survival rates, but early diagnosis is crucial for improving outcomes and awareness of risk factors is vital for early diagnosis. Cytotoxic chemotherapy is the cornerstone of treatment for advanced or metastatic cases, although molecularly targeted therapies and immunotherapies may benefit select patients. Treatment selection depends on several factors, including patients' performance status and co-morbidities and these should be considered alongside the efficacy and safety profiles of the different chemotherapy regimens. This 2-part microlearning provides an overview of the risk factors, diagnostic tools and treatment options available to date for different patient groups. Complete both modules, answer pre- and post-test questions and start earning CME credits. This programme is also featured on the COR2ED website, here: Metastatic pancreatic ductal adenocarcinoma (PDAC): from diagnosis to treatment

Guest: Efrat Dotan, MD Guest: Shubham Pant, MD, MBBS Pancreatic ductal adenocarcinoma, otherwise known as PDAC, is a lethal disease which is usually diagnosed at an advanced stage and has an extremely poor prognosis. Advancements in treatment regimens have improved survival rates, but early diagnosis is crucial for improving outcomes and awareness of risk factors is vital for early diagnosis. Cytotoxic chemotherapy is the cornerstone of treatment for advanced or metastatic cases, although molecularly targeted therapies and immunotherapies may benefit select patients. Treatment selection depends on several factors, including patients' performance status and co-morbidities and these should be considered alongside the efficacy and safety profiles of the different chemotherapy regimens. This 2-part microlearning provides an overview of the risk factors, diagnostic tools and treatment options available to date for different patient groups. Complete both modules, answer pre- and post-test questions and start earning CME credits. This programme is also featured on the COR2ED website, here: Metastatic pancreatic ductal adenocarcinoma (PDAC): from diagnosis to treatment

Guest: Efrat Dotan, MD Guest: Shubham Pant, MD, MBBS Pancreatic ductal adenocarcinoma, otherwise known as PDAC, is a lethal disease which is usually diagnosed at an advanced stage and has an extremely poor prognosis. Advancements in treatment regimens have improved survival rates, but early diagnosis is crucial for improving outcomes and awareness of risk factors is vital for early diagnosis. Cytotoxic chemotherapy is the cornerstone of treatment for advanced or metastatic cases, although molecularly targeted therapies and immunotherapies may benefit select patients. Treatment selection depends on several factors, including patients' performance status and co-morbidities and these should be considered alongside the efficacy and safety profiles of the different chemotherapy regimens. This 2-part microlearning provides an overview of the risk factors, diagnostic tools and treatment options available to date for different patient groups. Complete both modules, answer pre- and post-test questions and start earning CME credits. This programme is also featured on the COR2ED website, here: Metastatic pancreatic ductal adenocarcinoma (PDAC): from diagnosis to treatment

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

In this episode Liz and Jesse are joined once again for a great part 2 by Professor Ian Coombes. Ian is the Director of Pharmacy at RBWH and an expert in safety thinking. Ian looks at the what and why of the most common error prone medication types. Ian's Five (Plus One) Things: Paracetamol and other analgesics, Insulin and other diabetic medicines. Heparin, enoxaparin and other anticoagulants. Antimicrobials. Cardiac medicines in the hospital setting. Cytotoxic drugs.

References Front Immunol. 2023; 14: 1151166. Dr Guerra: Biochemistry lecture archives Telemann, G.P. 1725.Viola Concerto in G major https://youtu.be/yMpzPMkrALM?si=lpyDYITx63jTc6-K --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

In the 26th episode of our Immunology 101 series, Ash and Jatin shift gears from humoral immunity to cellular immunity and discuss cytotoxic T cell activation.

Dr. Iyad Alnahhas interviews Drs. Maria Jose Contreras-Zarate and Diana Cittelly about their recent manuscript entitled: "Short-term topiramate treatment prevents radiation-induced cytotoxic edema in preclinical models of breast-cancer brain metastasis", published online in Neuro-Oncology in April 2023. Read Paper

In this Buddisode, we sit down with Drs. Cosima T Baldari & Rino Rappuoli to discuss their work on a unique immune evasion strategy deployed by SARS CoV2 to paralyze cytotoxic T cells.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.10.523231v1?rss=1 Authors: Abdelwahab, T., Stadler, D., Knopper, K., Arampatzi, P., Saliba, A.-E., Kastenmuller, W., Martini, R., Groh, J. Abstract: Myelin defects lead to neurological dysfunction in various diseases and in normal aging. Chronic neuroinflammation often contributes to axon-myelin damage in these conditions and can be initiated and/or sustained by perturbed myelinating glia. We have previously shown that distinct mutations in the PLP1 gene result in neurodegeneration that is largely driven by adaptive immune cells. Here we characterize CD8+ CNS-associated T cells in these myelin mutants using single-cell transcriptomics and identify population heterogeneity and disease-associated changes. We demonstrate that early sphingosine-1-phosphate receptor modulation attenuates the recruitment of T cells and neural damage, while later targeting of CNS-associated T cell populations is inefficient and has no effect on neurodegeneration. Applying bone marrow chimerism and utilizing random X chromosome inactivation, we provide evidence that axonal damage is driven by cytotoxic, antigen specific CD8+ T cells that target mutant myelinating oligodendrocytes. These findings offer insights into neural-immune interactions and are of translational relevance for neurological conditions associated with myelin defects and neuroinflammation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.13.512083v1?rss=1 Authors: Lanteri, M. L., Silveyra, M. X., Moran, M. M., Boutet, S., Solis-Gozar, D.-D., Perreau, F., Andreu, A. B. Abstract: Andean potatoes (Solanum tuberosum L. ssp. andigena) are a good source of dietary antioxidant polyphenols. We have previously demonstrated that polyphenol extracts from Andean potato tubers exerted a dose-dependent cytotoxic effect in human neuroblastoma SH-SY5Y cells, being skin extracts more potent than flesh ones. In order to gain insight into the bioactivities of potato phenolics, we investigated the composition and the in vitro cytotoxic activity of total extracts and fractions of skin and flesh tubers of three Andean potato cultivars (Santa Maria, Waicha, and Moradita). Potato total extracts were subjected to liquid-liquid fractionation using ethyl acetate solvent in organic and aqueous fractions. We analyzed both fractions by HPLC-DAD, HPLC-ESI-MS/MS, and HPLC-HRMS. Results corroborated the expected composition of each fraction. Organic fractions were rich in hydroxycinnamic acids (principally chlorogenic acid isomers), whereas aqueous fractions contained mainly polyamines conjugated with phenolic acids, glycoalkaloids, and flavonoids. Organic fractions were not cytotoxic against SH-SY5Y cells, and indeed, some increased cellular metabolism compared to controls. Aqueous fractions were cytotoxic and even more potent than their respective total extracts. Treatment with a combination of both fractions showed a similar cytotoxic response to the corresponding extract. According to correlation studies, it is tempting to speculate that polyamines and glycoalkaloids are crucial in inducing cell death. Our findings indicate that the activity of Andean potato extracts is a combination of various compounds and contribute to the revalorization of potato as a functional food. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

On Episode 4 of the Conscious Breathing Podcast with Steve Scott, Dr. Daniel Thomas shows us the next-generation strategies he is successfully using with his cancer patients who come from all over the world to get treatment from him at his medical clinic in the Orlando Florida area.    Dr. Thomas is a highly educated, experienced, and forward-thinking physician. For over 30 years, he has helped people all over the world by providing innovative solutions to reverse disease, improve mental and physical vigor, and increase lifespan. His expertise is in the practical application of cutting-edge biomedical research. Dr. Thomas spends 20-30 hours a week poring over the latest scientific literature in search of promising therapeutic strategies.   In this show, he goes over his 8 step treatment protocol. You'll learn why the most aggressive tumors are hypoxic and how carbon dioxide treatments may be an effective tool in the battle against cancer.    If you or a loved one has cancer, make sure to listen to the entire show and learn some strategies you may have never heard of before.    00:00:00 Introduction  00:01:19 Breathing with the Relaxator 00:01.51 Introducing Dr. Daniel Thomas 00:02:53 Dr. Daniels Tomas' background & how he got interested in cancer 00:04:39 The reason for reading science journals instead of medical journals 00:05:48 The Gerson Institute nutritional therapy  00:06:39 The history of the Gerson Therapy 00:09:37 What is the cause of cancer? Genomic vs metabolic 00:11:31 Recent discovery - cancer's love affair of iron 00:12:33 Cancer & iron levels, absorption & excretion 00:13:56 Could high iron levels be a potential sign of cancer? 00:15:12 Optimal ferritin levels 00:15:46 The benefit of blood donation in reducing iron levels & the advantage of female menstruation, especially for protecting the heart 00:16:40 Pulling down iron levels with natural supplementation & commercial drugs  00:18:03 Excess iron & genetic mutations. Iron's role in assisting or magnifying cancer's ability to get the energy it needs, especially from glucose 00:19:15 Cancer's need for glucose & how cancer gets its energy. Glutamine, fatty acids & autophagy. 00:21:09 Glycolysis vs aerobic use of sugar & The “Warburg Effect” 00:22:36 The use of carbon dioxide in cancer treatment – BodyStream & Carbohaler.  Hypoxia & Normaxia. Tumor & tissue oxygenation. Bohr Effect.  00:25:08 Preferences for how to use carbon dioxide for different types of cancer, topically (BodyStream) vs inhalation (Carbohaler) 00:27:01 Breathing methods & the importance of oxygenating the cancer tumor to make it vulnerable. IV therapies. Ozonated salin. Increasing efficacy of chemotherapy & radiation.  00:29:04 Hyperthermia & heating tumor tissue for increased blood flow & delivery of chemo drugs or natural compounds. Cytotoxic effect.  00:30:57 How heat affects hemoglobin's affinity for oxygen.  00:31:59 Dr. Daniel's protocols for the cancer patients that seek him out & why patients usually get the best results when combining conventional & alternative medicine. Reducing risk of developing chemo resistance & radio resistance   00:35:02 Next generation medicine, going beyond alternative medicine & blending the best of both worlds. Functional medicine. Integrative medicine.   00:37:04 Diet & cancer. The use of repurposed medicine, Ivermectin. A twofold approach.     00:39:23 Hyperthermia. The procedure of heating up the cancer tumor   00:41:02 Benefits of regular sauna & infrared sauna in comparison to medical hyperthermia machines?    00:42:07 What is more important - treating the whole person (environment of tumor), vs the tumor itself? Dr. Daniel's eightfold approach to cancer treatment   00:43:54 The role of the essential amino acid methionine & why Dr. Daniel advocates for a plant based diet for most cancer patients    00:46:19 Dr. Daniel's walks us through his eightfold approach to treating cancer  First approach – to target cancer's addiction to methionine & iron & its resistance to ferroptosis (iron mediated cell death)   00:47:50 Second approach –to inhibit cancer's ability to metabolize glucose or glutamine for energy. Metformin. Sodium selenite.   00:49:03 Recent data on shutting down fat metabolism by cancer   00:50:25 Third approach – Increasing tumor blood flow & reducing tumor hypoxia    00:51:08 Fourth approach – Lowering inflammatory markers 00:51:39 Fifth approach – Immunotherapy. Stimulating the immune system & removing the barriers that can inhibit a strong immune system from working   00:52:14 Sixth approach – Suppressing the metastatic potential of cancer. Help preventing the lymphatic system from spreading the cancer. The reason people die from cancer & the use of lithium.   00:53:29 Seventh approach – The importance of not only targeting cancer cells, but also cancer stem cells.    00:53:43 Eight approach – Promoting efficient removal of tumor debris & and how your body removes the tumor debris   00:54:56 The different stages of cancer. The possibility of integrating conventional therapies with alternative therapies & the reason for Dr. Daniel's high success rate    00:58:02 The importance of hope in people's success rate   01:00:21 Having a student's perspective & being open minded   01:01:34 Solasonin & solamargin, natural compounds found in eggplant that potentially can work as strong as chemo & might give lasting immunity to cancer    01:04:07 Plant compounds may hold the key to all ills of mankind   01:04:57 Different approaches for different types of cancer   01:07:43 The different treatment options offered at Dr. Daniel Thomas' clinic & how to get in touch.

Covid Vaccine Spike Protein is Very Dangerous- it's Cytotoxic and Why Effective Treatments Are Being Suppressed.   Spike protein is very dangerous, it's cytotoxic (Robert Malone, Steve Kirsch, Bret Weinstein) Why is this treatment being suppressed? (Pierre Kory & Bret Weinstein)   Spike protein is very dangerous, it's cytotoxic (Robert Malone, Steve Kirsch, Bret Weinstein) https://youtu.be/Du2wm5nhTXY DarkHorse Podcast Clips 162K subscribers Spike protein is very dangerous, it's cytotoxic. Dr. Robert Malone is the inventor of mRNA Vaccine technology. Mr. Steve Kirsch is a serial entrepreneur who has been researching adverse reactions to COVID vaccines. Bret talks to Robert and Steve about the pandemic, treatment and the COVID vaccines. Steve's paper on COVID vaccine reactions: https://trialsitenews.com/should-you-... Steve's Twitter: https://twitter.com/stkirsch COVID-19 Early Treatment Fund: https://www.treatearly.org/team/steve... Dr. Malone's website: https://www.rwmalonemd.com/mrna-vacci... Robert's LinkedIn profile: https://www.linkedin.com/in/rwmalonemd Robert's Twitter: https://twitter.com/RWMaloneMD Find Bret Weinstein on Twitter: @BretWeinstein, and on Patreon. https://www.patreon.com/bretweinstein https://twitter.com/BretWeinstein Please subscribe to this channel for more long form content like this, and subscribe to the clips channel @DarkHorse Podcast Clips for short clips of all our podcasts. DarkHorse merchandise now available at: store.darkhorsepodcast.org Clip from DarkHorse podcast. Full livestream here: https://youtu.be/-_NNTVJzqtY Bitchute for backup: https://www.bitchute.com/video/TH2HAm...   Why is this treatment being suppressed? (Pierre Kory & Bret Weinstein) https://youtu.be/q01LUg97eto 65,187 views DarkHorse Podcast Clips 162K subscribers Why is this COVID treatment being suppressed? Clip from Bret Weinstein and Pierre Kory on DarkHorse - CENSORED on YouTube - available on Spotify or here: https://www.bitchute.com/video/qHjNQI... 00:00 Disclaimer 01:33 Clip starts On this very special live broadcast of the DarkHorse podcast, Dr. Bret Weinstein (Ph.D) and Dr. Pierre Kory (M.D.) will discuss the ongoing pandemic, the care of COVID-19 patients, and the incredible story of Ivermectin. Mentioned in the full episode: British Ivermectin Recommendation Development group: https://bird-group.org The BIRD Recommendation on the Use of Ivermectin for Covid-19: Executive Summary: https://bird-group.org/wp-content/upl... Carvallo et al 2020. Study of the efficacy and safety of topical ivermectin+ iota-carrageenan in the prophylaxis against COVID-19 in health personnel. J. Biomed. Res. Clin. Investig., 2. https://medicalpressopenaccess.com/up... Cobos-Campos et al 2021.Potential use of ivermectin for the treatment and prophylaxis of SARS-CoV-2 infection: Efficacy of ivermectin for SARS-CoV-2. Clin Res Trials, 7: 1-5. https://www.readkong.com/page/potenti... Database of all ivermectin COVID-19 studies. 93 studies, 55 peer reviewed, 56 with results comparing treatment and control groups: https://c19ivermectin.com Karale et al 2021. A Meta-analysis of Mortality, Need for ICU admission, Use of Mechanical Ventilation and Adverse Effects with Ivermectin Use in COVID-19 Patients. medRxiv. https://www.medrxiv.org/content/medrx... Kory et al 2021. Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19. American Journal of Therapeutics, 28(3): e299: https://www.ncbi.nlm.nih.gov/pmc/arti... Nardelli et al 2021. Crying wolf in time of Corona: the strange case of ivermectin and hydroxychloroquine. Is the fear of failure withholding potential life-saving treatment from clinical use?. Signa Vitae, 1: 2. https://oss.signavitae.com/mre-signav... Yagisawa et al 2021. Global trends in clinical studies of ivermectin in COVID-19. The Japanese Journal of Antibiotics, 74: 1. https://www.psychoactif.org/forum/upl... --- The FLCCC: https://covid19criticalcare.com/ Dr. Kory on Twitter: @PierreKory --- Find Bret Weinstein on Twitter: @BretWeinstein, and on Patreon. Please subscribe to this channel for more long form content like this, and subscribe to the clips channel @DarkHorse Podcast Clips for short clips of all our podcasts. DarkHorse merchandise now available at: store.darkhorsepodcast.org     From Trial Site News-   Should you get vaccinated? Steve KirschMay 25, 2021 I always get vaccinated. I have been fully vaccinated with the Moderna COVID vaccine. My three daughters have all been vaccinated. I recently learned that these vaccines have killed over 25,800 Americans and disabled at least 1,000,000 more. And we're only halfway to the finish line. We need to PAUSE these vaccines NOW before more people are killed. Based on what I now know about the miniscule vaccine benefits (approximately a .3% reduction in absolute risk), side effects (including death), current COVID rates, and the success rate of early treatment protocols, the answer I would give today to anyone asking me for advice as to whether to take any of the current vaccines would be, “Just say NO.” The current vaccines are particularly contraindicated if you have already been infected with COVID or are under age 20. For these people, I would say “NO! NO! NO!” In this article, I will explain what I have learned since I was vaccinated that totally changed my mind. You will learn how these vaccines work and the shortcuts that led to the mistakes that were made. You will understand why there are so many side effects and why these are so varied and why they usually happen within 30 days of vaccination. You will understand why kids are having heart issues (for which there is no treatment), and temporarily losing their sight, and ability to talk. You will understand why as many as 3% may be severely disabled by the vaccine. What I find deeply disturbing is the lack of transparency on how dangerous the current COVID vaccines are. Healthy people could end up dead or permanently disabled at a rate that is “off the charts” compared with any other vaccine in our history. Look at the death report in our government's official Vaccine Adverse Event Reporting System (VAERS) summarized in the tweet below. This is the most deadly vaccine we've ever made by a long shot. That's why they have to give you incentives to get vaccinated. They need to vaccinate everyone BEFORE people read this article or watch this video of Dr. Peter McCullough explaining clearly why the current COVID vaccines are unsafe and completely unnecessary for our children. The death rate from this vaccine is off the charts, more than all 70 vaccines over the past 30 years combined But this is just the beginning of our story. We have a lot of ground to cover. I'll talk about Fauci, NIAID, CDC, Congress, academia, Cliff Lane, and more . Before we jump into the details, here are some key points: At least 6,000 deaths from the vaccine. The OpenVAERS team think it is over 20,000 due to under reporting. Biodistribution data shows massive accumulation in ovaries of the LNP (which instructs cells in ovaries to sprout toxic spike protein). Whoops. That was never supposed to be leaked out. We obtained it via FOIA request. The CDC never told you about that one, did they? Of course not! 82% miscarriage rate in first 20 weeks (10% is the normal rate). It is baffling that the CDC says the vaccine is safe for pregnant women when it is so clear that this is not the case. For example, one our family friends is a victim of this. She miscarried at 25 weeks and is having an abortion on 6/9/21. She had her first shot 7 weeks ago, and her second shot 4 weeks ago. The baby had severe bleeding of the brain and other disfigurements. Her gynecologist had never seen anything like that before in her life. They called in a specialist who said it was probably a genetic defect (because everyone buys into the narrative that the vaccine is safe it is always ruled out as a possible cause). No VAERS report. No CDC report. Yet the doctors I've talked to say that it is over 99% certain it was the vaccine. The family doesn't want an autopsy for fear that their daughter will find out it was the vaccine. This is a perfect example of how these horrible side effects just never get reported anywhere. 25X the possibility of myocarditis for teen boys (can lead to heart failure and death) Kids already have natural immunity (Science Magazine article), so there is no benefit to vaccination, only risk. Have you ever seen the risk / benefit analysis by the CDC?? Ask for it before you consent. No point vaccinating those who've had COVID-19: Findings of Cleveland Clinic study. No benefit, only risk. Doctors who attribute adverse events to the vaccine are punished (such as Dr. Hoffe). So under reporting is incentivized. The CDC refuses to say how many people have died and is “still investigating” heart damage in kids even though it is obvious why (free spike protein causing clotting and inflammation). A 25X increase when the only “new” thing is the vaccine isn't hard to figure out. Ask the CDC for their current top 5 hypotheses for the cause. It will be more than amusing to see what they say. If it isn't the vaccine, heads should roll. The CDC is deliberately misleading the American people. Check out the side effects page. Death, disability, excessive miscarriage rates, heart attacks, stroke, inability to walk, talk, or see, Bell's Palsy, persistent pain, Parkinson's like symptoms, re-activation of shingles, blood clots, etc. are all missing. >500X more deadly than the flu vaccine COVID vaccines have generated more adverse reports in the last 6 months than all 70 vaccines over the past 30 years combined. They missed that one. Defective virus design (s1 was never supposed to be free, inclusion of PEG was unnecessary and allows LNP to be widely distributed) Strong opposition to vaccination by extremely credible voices like Malone, Geert Vanden Bossche, others NIAID (Cliff Lane) is improperly manipulating the COVID Treatment Guidelines to make it appear these drugs do not work, thus giving the world the false impression that the vaccine, even if imperfect, is the only way out. Ivermectin and fluvoxamine have been confirmed in Phase 3 trials. Ivermectin has a very high quality systematic review, the highest possible level in Evidence Based Medicine. Repurposed drugs are safer and more effective than the current vaccines. In general, early treatment with an effective protocols reduce your risk of dying by more than 100X so instead of 600,000 deaths, we'd have fewer than 6,000 deaths. NOTE: The vaccine has already killed over 6,000 people and that's from the vaccine alone (and doesn't count any breakthrough deaths). Vaccines skipped proper toxicology studies in order to bring to market faster. We don't know what we don't know. The unpredictable and horrifying side effects of this vaccine on heathy kids, such as the 16 year old girl who was unable to speak and see just 48 hours after being vaccinated Debilitating side effects can happen at any time because vaccine victims are very similar to COVID long haulers (Dr. Bruce Patterson has discovered this) and we all know that long haul can start at anytime (even when the disease is asymptomatic) and could be incurable. Because the vaccine is not perfectly safe, the government is required by law to warn people of the death and disability risks caused by the vaccine and to obtain informed consent. Always be sure to ask for the 50 most serious side effects and how often they happen. And find out whether they will compensate you if you are disabled for life from the vaccine. This is important because the blood clots can form anywhere with this very unsafe virus. Note: this is a large document and different sections were written at different times so you may find that the numbers may be inconsistent. If you spot an error, please use the comments to point it out. If you enjoyed reading this article, please follow me on Twitter at @stkirsch so I can keep you apprised of how this story progresses. The more followers I have, the less likely they will ignore my requests for informed consent and data transparency. Also, please share with your friends on social media. Thanks! New research shows why we should not vaccinate kids Will we listen to the SCIENCE? Or will will follow the Biden, CDC, NIH narrative blindly? Time to decide.

Covid Vaccine Spike Protein is Very Dangerous- it's Cytotoxic and Why Effective Treatments Are Being Suppressed.   Spike protein is very dangerous, it's cytotoxic (Robert Malone, Steve Kirsch, Bret Weinstein) Why is this treatment being suppressed? (Pierre Kory & Bret Weinstein)   Spike protein is very dangerous, it's cytotoxic (Robert Malone, Steve Kirsch, Bret Weinstein) https://youtu.be/Du2wm5nhTXY DarkHorse Podcast Clips 162K subscribers Spike protein is very dangerous, it's cytotoxic. Dr. Robert Malone is the inventor of mRNA Vaccine technology. Mr. Steve Kirsch is a serial entrepreneur who has been researching adverse reactions to COVID vaccines. Bret talks to Robert and Steve about the pandemic, treatment and the COVID vaccines. Steve's paper on COVID vaccine reactions: https://trialsitenews.com/should-you-... Steve's Twitter: https://twitter.com/stkirsch COVID-19 Early Treatment Fund: https://www.treatearly.org/team/steve... Dr. Malone's website: https://www.rwmalonemd.com/mrna-vacci... Robert's LinkedIn profile: https://www.linkedin.com/in/rwmalonemd Robert's Twitter: https://twitter.com/RWMaloneMD Find Bret Weinstein on Twitter: @BretWeinstein, and on Patreon. https://www.patreon.com/bretweinstein https://twitter.com/BretWeinstein Please subscribe to this channel for more long form content like this, and subscribe to the clips channel @DarkHorse Podcast Clips for short clips of all our podcasts. DarkHorse merchandise now available at: store.darkhorsepodcast.org Clip from DarkHorse podcast. Full livestream here: https://youtu.be/-_NNTVJzqtY Bitchute for backup: https://www.bitchute.com/video/TH2HAm...   Why is this treatment being suppressed? (Pierre Kory & Bret Weinstein) https://youtu.be/q01LUg97eto 65,187 views DarkHorse Podcast Clips 162K subscribers Why is this COVID treatment being suppressed? Clip from Bret Weinstein and Pierre Kory on DarkHorse - CENSORED on YouTube - available on Spotify or here: https://www.bitchute.com/video/qHjNQI... 00:00 Disclaimer 01:33 Clip starts On this very special live broadcast of the DarkHorse podcast, Dr. Bret Weinstein (Ph.D) and Dr. Pierre Kory (M.D.) will discuss the ongoing pandemic, the care of COVID-19 patients, and the incredible story of Ivermectin. Mentioned in the full episode: British Ivermectin Recommendation Development group: https://bird-group.org The BIRD Recommendation on the Use of Ivermectin for Covid-19: Executive Summary: https://bird-group.org/wp-content/upl... Carvallo et al 2020. Study of the efficacy and safety of topical ivermectin+ iota-carrageenan in the prophylaxis against COVID-19 in health personnel. J. Biomed. Res. Clin. Investig., 2. https://medicalpressopenaccess.com/up... Cobos-Campos et al 2021.Potential use of ivermectin for the treatment and prophylaxis of SARS-CoV-2 infection: Efficacy of ivermectin for SARS-CoV-2. Clin Res Trials, 7: 1-5. https://www.readkong.com/page/potenti... Database of all ivermectin COVID-19 studies. 93 studies, 55 peer reviewed, 56 with results comparing treatment and control groups: https://c19ivermectin.com Karale et al 2021. A Meta-analysis of Mortality, Need for ICU admission, Use of Mechanical Ventilation and Adverse Effects with Ivermectin Use in COVID-19 Patients. medRxiv. https://www.medrxiv.org/content/medrx... Kory et al 2021. Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19. American Journal of Therapeutics, 28(3): e299: https://www.ncbi.nlm.nih.gov/pmc/arti... Nardelli et al 2021. Crying wolf in time of Corona: the strange case of ivermectin and hydroxychloroquine. Is the fear of failure withholding potential life-saving treatment from clinical use?. Signa Vitae, 1: 2. https://oss.signavitae.com/mre-signav... Yagisawa et al 2021. Global trends in clinical studies of ivermectin in COVID-19. The Japanese Journal of Antibiotics, 74: 1. https://www.psychoactif.org/forum/upl... --- The FLCCC: https://covid19criticalcare.com/ Dr. Kory on Twitter: @PierreKory --- Find Bret Weinstein on Twitter: @BretWeinstein, and on Patreon. Please subscribe to this channel for more long form content like this, and subscribe to the clips channel @DarkHorse Podcast Clips for short clips of all our podcasts. DarkHorse merchandise now available at: store.darkhorsepodcast.org     From Trial Site News-   Should you get vaccinated? Steve KirschMay 25, 2021 I always get vaccinated. I have been fully vaccinated with the Moderna COVID vaccine. My three daughters have all been vaccinated. I recently learned that these vaccines have killed over 25,800 Americans and disabled at least 1,000,000 more. And we're only halfway to the finish line. We need to PAUSE these vaccines NOW before more people are killed. Based on what I now know about the miniscule vaccine benefits (approximately a .3% reduction in absolute risk), side effects (including death), current COVID rates, and the success rate of early treatment protocols, the answer I would give today to anyone asking me for advice as to whether to take any of the current vaccines would be, “Just say NO.” The current vaccines are particularly contraindicated if you have already been infected with COVID or are under age 20. For these people, I would say “NO! NO! NO!” In this article, I will explain what I have learned since I was vaccinated that totally changed my mind. You will learn how these vaccines work and the shortcuts that led to the mistakes that were made. You will understand why there are so many side effects and why these are so varied and why they usually happen within 30 days of vaccination. You will understand why kids are having heart issues (for which there is no treatment), and temporarily losing their sight, and ability to talk. You will understand why as many as 3% may be severely disabled by the vaccine. What I find deeply disturbing is the lack of transparency on how dangerous the current COVID vaccines are. Healthy people could end up dead or permanently disabled at a rate that is “off the charts” compared with any other vaccine in our history. Look at the death report in our government's official Vaccine Adverse Event Reporting System (VAERS) summarized in the tweet below. This is the most deadly vaccine we've ever made by a long shot. That's why they have to give you incentives to get vaccinated. They need to vaccinate everyone BEFORE people read this article or watch this video of Dr. Peter McCullough explaining clearly why the current COVID vaccines are unsafe and completely unnecessary for our children. The death rate from this vaccine is off the charts, more than all 70 vaccines over the past 30 years combined But this is just the beginning of our story. We have a lot of ground to cover. I'll talk about Fauci, NIAID, CDC, Congress, academia, Cliff Lane, and more . Before we jump into the details, here are some key points: At least 6,000 deaths from the vaccine. The OpenVAERS team think it is over 20,000 due to under reporting. Biodistribution data shows massive accumulation in ovaries of the LNP (which instructs cells in ovaries to sprout toxic spike protein). Whoops. That was never supposed to be leaked out. We obtained it via FOIA request. The CDC never told you about that one, did they? Of course not! 82% miscarriage rate in first 20 weeks (10% is the normal rate). It is baffling that the CDC says the vaccine is safe for pregnant women when it is so clear that this is not the case. For example, one our family friends is a victim of this. She miscarried at 25 weeks and is having an abortion on 6/9/21. She had her first shot 7 weeks ago, and her second shot 4 weeks ago. The baby had severe bleeding of the brain and other disfigurements. Her gynecologist had never seen anything like that before in her life. They called in a specialist who said it was probably a genetic defect (because everyone buys into the narrative that the vaccine is safe it is always ruled out as a possible cause). No VAERS report. No CDC report. Yet the doctors I've talked to say that it is over 99% certain it was the vaccine. The family doesn't want an autopsy for fear that their daughter will find out it was the vaccine. This is a perfect example of how these horrible side effects just never get reported anywhere. 25X the possibility of myocarditis for teen boys (can lead to heart failure and death) Kids already have natural immunity (Science Magazine article), so there is no benefit to vaccination, only risk. Have you ever seen the risk / benefit analysis by the CDC?? Ask for it before you consent. No point vaccinating those who've had COVID-19: Findings of Cleveland Clinic study. No benefit, only risk. Doctors who attribute adverse events to the vaccine are punished (such as Dr. Hoffe). So under reporting is incentivized. The CDC refuses to say how many people have died and is “still investigating” heart damage in kids even though it is obvious why (free spike protein causing clotting and inflammation). A 25X increase when the only “new” thing is the vaccine isn't hard to figure out. Ask the CDC for their current top 5 hypotheses for the cause. It will be more than amusing to see what they say. If it isn't the vaccine, heads should roll. The CDC is deliberately misleading the American people. Check out the side effects page. Death, disability, excessive miscarriage rates, heart attacks, stroke, inability to walk, talk, or see, Bell's Palsy, persistent pain, Parkinson's like symptoms, re-activation of shingles, blood clots, etc. are all missing. >500X more deadly than the flu vaccine COVID vaccines have generated more adverse reports in the last 6 months than all 70 vaccines over the past 30 years combined. They missed that one. Defective virus design (s1 was never supposed to be free, inclusion of PEG was unnecessary and allows LNP to be widely distributed) Strong opposition to vaccination by extremely credible voices like Malone, Geert Vanden Bossche, others NIAID (Cliff Lane) is improperly manipulating the COVID Treatment Guidelines to make it appear these drugs do not work, thus giving the world the false impression that the vaccine, even if imperfect, is the only way out. Ivermectin and fluvoxamine have been confirmed in Phase 3 trials. Ivermectin has a very high quality systematic review, the highest possible level in Evidence Based Medicine. Repurposed drugs are safer and more effective than the current vaccines. In general, early treatment with an effective protocols reduce your risk of dying by more than 100X so instead of 600,000 deaths, we'd have fewer than 6,000 deaths. NOTE: The vaccine has already killed over 6,000 people and that's from the vaccine alone (and doesn't count any breakthrough deaths). Vaccines skipped proper toxicology studies in order to bring to market faster. We don't know what we don't know. The unpredictable and horrifying side effects of this vaccine on heathy kids, such as the 16 year old girl who was unable to speak and see just 48 hours after being vaccinated Debilitating side effects can happen at any time because vaccine victims are very similar to COVID long haulers (Dr. Bruce Patterson has discovered this) and we all know that long haul can start at anytime (even when the disease is asymptomatic) and could be incurable. Because the vaccine is not perfectly safe, the government is required by law to warn people of the death and disability risks caused by the vaccine and to obtain informed consent. Always be sure to ask for the 50 most serious side effects and how often they happen. And find out whether they will compensate you if you are disabled for life from the vaccine. This is important because the blood clots can form anywhere with this very unsafe virus. Note: this is a large document and different sections were written at different times so you may find that the numbers may be inconsistent. If you spot an error, please use the comments to point it out. If you enjoyed reading this article, please follow me on Twitter at @stkirsch so I can keep you apprised of how this story progresses. The more followers I have, the less likely they will ignore my requests for informed consent and data transparency. Also, please share with your friends on social media. Thanks! New research shows why we should not vaccinate kids Will we listen to the SCIENCE? Or will will follow the Biden, CDC, NIH narrative blindly? Time to decide.

Trimester 1,2,3,4,5- Pregnancy and Beyond, You can Survive The first trimester is the earliest phase of pregnancy. It starts on the first day of your last period -- before you're even actually pregnant -- and lasts until the end of the 13th week. The changing body 1. Fatigue 2. Morning sickness 3. Breast tenderness 4. Bleeding Emergency Symptoms During the First Trimester 1. Severe abdominal pain 2. Heavy bleeding 3. Severe dizziness 4. Rapid weight gain or too little weight gain Prenatal vitamin   Ob-Gyn visits What/how much should I eat during pregnancy? Exercise Avoid putting pressure on your abdomen. Get rest and move your body to keep your muscles healthy. Bring up any concerns with your doctor.   Cases to avoid? 1. Total joints- Bone cement aka methyl methacrylate- O2 mask, Z 2. Radiation- maximal fetal dose should not exceed 0.5 rem/ 50mrem/ month- ionizing radiation XRAY, IR-->double lead, step out, fetal dosimeter 3. Cytotoxic agents- chemotherapy, HIPEC 4. Peds- inhaled inductions with nitrous 5. CMV - Transplant cases 6. Extracorporeal shockwave lithotripsy (ESWL) --Noise→ fetal hearing Childcare- nanny vs daycare 1. Consider your lifestyle and specific needs 2. Get childcare lined up ASAP, especially if you live in a big city Maternity leave/ FMLA rules 1. Do research on your hours etc. early on to take care of future you   Send an email to: Hello@anesthesiamom.com IG: @Stethoscopes.to.Swaddles Please leave a review, it helps the show so much Information sources: pregnancy-info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.13.381988v1?rss=1 Authors: Saumya, K. U., Gadhave, K., Kumar, A., Giri, R. Abstract: Capsid-anchor (CA) of Zika virus (ZIKV) is a small, single-pass transmembrane sequence that separates the capsid (C) protein from downstream pre-membrane (PrM) protein. During ZIKV polyprotein processing, CA is cleaved-off from C and PrM and left as a membrane-embedded peptide. CA plays an essential role in the assembly and maturation of the virus. However, its independent folding behavior is still unknown. Since misfolding and aggregation propensity of transmembrane proteins are now increasingly recognized and has been linked to several proteopathic disorders. Therefore, in this study, we investigated the amyloid-forming propensity of CA at physiological conditions. We observed aggregation behavior of CA peptide using dye-binding assays and ThT kinetics. The morphological analysis of CA aggregates explored by high-resolution microscopy (TEM and AFM) revealed characteristic amyloid-like fibrils. Further, the effect on mammalian cells exhibited the cytotoxic nature of the CA amyloid-fibrils. Our findings collectively shed light on the amyloidogenic phenomenon of flaviviral protein, which may contribute to their infection. Copy rights belong to original authors. Visit the link for more info

Traditional Approach:   Secretory -- poisoned mucosal villi -- "the sieve" Cytotoxic -- destroyed mucosal villi -- "the shred" Osmotic -- malabsorption -- "the pull" Inflammatory -- edema, motility -- "the push" Lots of overlap, difficult to apply to clinical signs and symptoms.   Bedside Approach: Fever/No Fever, Bloody/No Blood   Non-bloody, febrile -- most likely viral Non-bloody, afebrile -- may be viral Bloody, febrile -- likely bacterial Non-bloody, afebrile -- full stop.  Eval for Hemolytic Uremic Syndrome   Workup   Ask yourself -- again -- why is this not... appendicitis-torsion-intussusception-etc. Admit sick children, but most go home, so...   Non-bloody, febrile -- no workup necessary; precautionary advice  Non-bloody, afebrile -- be more skeptical, but generally same as above Bloody, febrile -- stool culture, follow up; do not treat empirically unless septic and admitted.  Culture will dictate treat/no treat/how. Bloody, afebrile -- evaluate for hemolytic uremic syndrome, especially if under 5 years old: CBC, chemistries, UA, stool culture   Evaluate Hydration Status                 Selected References Khan WA et al. Central Nervous System Manifestations of Childhood Shigellosis: Prevalence, Risk Factors, and Outcome. Pediatrics. 1999 Feb;103(2):E18 Lee JY et al. Diagnostic yield of stool culture and predictive factors for positive culture in patients with diarrheal illness. Medicine (Baltimore). 2017 Jul; 96(30): e7641. Nelson JD et al. Treatment of Salmonella gastroenteritis with ampicillin, amoxicillin, or placebo. Pediatrics 1980; 65:1125.        

Kimberly was a member of the Dr. Joanna Burdette lab and worked on projects related to the origins of ovarian cancer. She also discusses the learning curve of being a new member of a research lab. Kimberly's citations: Ren, Y., Ribas, H. T., Heath, K., Wu, S., Ren, J., Shriwas, P., & Kinghorn, A. D. (2020). Na+/K+-ATPase-Targeted Cytotoxicity of (+)-Digoxin and Several Semisynthetic Derivatives. Journal of Natural Products, 83(3), 638-648. [link] Hardy, L. R., Pergande, M. R., Esparza, K., Heath, K. N., Önyüksel, H., Cologna, S. M., & Burdette, J. E. (2019). Proteomic analysis reveals a role for PAX8 in peritoneal colonization of high grade serous ovarian cancer that can be targeted with micelle encapsulated thiostrepton. Oncogene, 38(32), 6003-6016. [link] Ren, Y., Tan, Q., Heath, K., Wu, S., Wilson, J. R., Ren, J., ... & Chen, X. (2020). Cytotoxic and non-cytotoxic cardiac glycosides isolated from the combined flowers, leaves, and twigs of Streblus asper. Bioorganic & Medicinal Chemistry, 115301. [link]

A look at this deadly mucocutaneous reaction and how to best manage these patients in the ED https://media.blubrry.com/coreem/content.blubrry.com/coreem/SJS.mp3 Download Leave a Comment Tags: Critical Care, Dermatology Show Notes Episode Produced by Audrey Bree Tse, MD Rash with dysuria should raise concern for SJS with associated urethritis Dysuria present in a majority of cases SJS is a mucocutaneous reaction caused by Type IV hypersensitivity Cytotoxic t-lymphocytes apoptose keratinocytes → blistering, bullae formation, and sloughing of the detached skin Disease spectrum SJS = 30% TBSA SJS/ TEN Overlap = 10-30% TBSA Incidence is estimated at around 9 per 1 million people in the US Mortality is 10% for SJS and 30-50% for TEN Mainly 2/2 sepsis and end organ dysfunction. SJS can occur even without a precipitating medication Infection can set it off especially in patients with risk factors including HIV, lupus, underlying malignancy, and genetic factors SATAN for the most common drugs Sulfa, Allopurinol, Tetracyclines, Anticonvulsants, and NSAIDS Anti-epileptics include carbamazepine, lamictal, phenobarb, and phenytoin Can have a curious course Hypersensitivity reaction can develop while taking medication, or even one to four weeks after exposure In pediatric population, mycoplasma pneumonia and herpes simplex have been identified as precipitating infections Patients often have a prodrome 1-3 days prior to the skin lesions appearing May complain of fever,

A look at this deadly mucocutaneous reaction and how to best manage these patients in the ED https://media.blubrry.com/coreem/content.blubrry.com/coreem/SJS.mp3 Download Leave a Comment Tags: Critical Care, Dermatology Show Notes Episode Produced by Audrey Bree Tse, MD Rash with dysuria should raise concern for SJS with associated urethritis Dysuria present in a majority of cases SJS is a mucocutaneous reaction caused by Type IV hypersensitivity Cytotoxic t-lymphocytes apoptose keratinocytes → blistering, bullae formation, and sloughing of the detached skin Disease spectrum SJS = 30% TBSA SJS/ TEN Overlap = 10-30% TBSA Incidence is estimated at around 9 per 1 million people in the US Mortality is 10% for SJS and 30-50% for TEN Mainly 2/2 sepsis and end organ dysfunction. SJS can occur even without a precipitating medication Infection can set it off especially in patients with risk factors including HIV, lupus, underlying malignancy, and genetic factors SATAN for the most common drugs Sulfa, Allopurinol, Tetracyclines, Anticonvulsants, and NSAIDS Anti-epileptics include carbamazepine, lamictal, phenobarb, and phenytoin Can have a curious course Hypersensitivity reaction can develop while taking medication, or even one to four weeks after exposure In pediatric population, mycoplasma pneumonia and herpes simplex have been identified as precipitating infections Patients often have a prodrome 1-3 days prior to the skin lesions appearing May complain of fever, myalgias,

This JCO Podcast provides observations and commentary on the JCO article Durable Tumor Regression and Overall Survival in Patients with Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy by Paul Nghiem, MD, PhD et al. My name is Reed Drews, and I am a member of the Cutaneous Oncology Program at Beth Israel Deaconess Medical Center in Boston, MA. My oncologic specialty is non-melanoma skin cancers.   Merkel cell carcinoma is a rare, aggressive neuroendocrine skin malignancy with high propensity for local recurrence and regional lymph node and systemic metastases. Its incidence rises exponentially with aging and is 10-fold higher in chronically immunosuppressed patients. When Merkel cell carcinoma is advanced and/or unresectable, historical 5-year overall survival rates are low, from 14 to 27%. Cytotoxic chemotherapies, like platinum plus etoposide used in other high-grade neuroendocrine malignancies, have not yielded durable response rates.   The cutaneous cell (or cells) of origin in Merkel cell carcinoma remains controversial. Nevertheless, scientists have identified 2 pathogenetic pathways leading to Merkel cell carcinoma. In 80% of cases, clonal integration of a polyomavirus leads to Merkel cell polyoma virus-positive Merkel cell carcinoma. In the other 20% of cases, ultraviolet light-induced DNA damage leads to polyoma virus-negative Merkel cell carcinoma. Polyoma virus-negative Merkel cell tumors display predominant cytosine to thymine transitions, a signature of DNA damage from UV light, and they have a 100-fold greater mutational burden than virus-positive Merkel cell cancers. For both subtypes, loss of immune surveillance, as with aging or chronic immunosuppression, contributes to Merkel cell carcinoma development, with diminished non-self-antigen recognition of UV-induced neo-antigens in virus-negative tumors and viral oncoproteins in Merkel cell polyoma virus-positive tumors.   Given these factors, investigators have recently studied whether immune checkpoint inhibitors might hold promise for managing advanced Merkel cell carcinoma. To date, 3 antibody inhibitors of the programmed cell death-1 pathway (abbreviated PD-1), including anti-PD-ligand-1 avelumab, anti-PD-1 nivolumab and anti-PD-1 pembrolizumab, have been tested in patients with chemotherapy-refractory and/or treatment naïve Merkel cell carcinoma. The 62% objective response rate from avelumab in treatment-naïve Merkel cell carcinoma was nearly twice that observed in chemotherapy-refractory disease. In 2017 avelumab became the first immune checkpoint inhibitor approved by the FDA for advanced Merkel cell carcinoma. Nivolumab yielded similar results, as did pembrolizumab according to a 2016 report from Nghiem and colleagues of a multicenter, phase 2, non-controlled study with 26 patients.   As reported in this JCO publication, Nghiem and colleagues have now increased their cohort to 50 patients through the multicenter expanded phase 2, Cancer Immunotherapy Trials Network-09/Keynote-017 trial. They administered pembrolizumab 2 mg/kg intravenously every 3 weeks for up to 2 years. Median follow-up time was 14.9 months, with a range from 0.4 to 36.4 months. This represents the longest follow-up to date of any anti-PD-1 pathway inhibitor for first-line treatment of advanced Merkel cell carcinoma. The 50-patient cohort included 43 patients with (stage IV) distant metastatic disease and 7 with stage IIIB recurrent locoregional disease not amenable to definitive surgery or radiation therapy. All patients had normal organ and bone marrow function and an Eastern Cooperative Oncology Group performance status of 0 to 1. Key exclusion criteria were previous systemic therapy for unresectable Merkel cell carcinoma, immunodeficiency or systemic immunosuppressive therapy, active autoimmune disease, concurrent second cancer, and active central nervous system metastases.   The median age of enrolled patients was 70.5 years, with 80% age 65 or older. 64% of patients had Merkel cell polyoma virus-positive tumors. For previous management of their primary Merkel cell carcinoma, 42 patients had had surgery, and 35 patients had had radiation treatment. While no patient had previously received systemic therapy for advanced Merkel cell carcinoma, 3 patients had received adjuvant chemotherapy greater than 6 months prior to study enrollment.   Patients received a median of 10.5 doses of pembrolizumab – range 1 to 35 doses—and the median treatment duration was 6.6 months – range 1 day to 23.6 months. Radiographic responses were assessed centrally per Response Evaluation Criteria in Solid Tumors, version 1.1. Responses were generally rapid and durable with 2.8 months as the median time to response – range 1.5 to 9.7 months. The objective response rate to pembrolizumab was 56%, with complete and partial responses of 24% and 32%, respectively; 10% had stable disease; and 32% had progressive disease.   At time of data analysis, 20 of 28 responses were on-going, and the median durability of response had not been reached. The Kaplan-Mier estimation of response durability at 24 months was 79.1%. Median progression free survival was 16.8 months, and the Kaplan-Mier estimation of progression free survival at 24 months was 48.3%. Median overall survival had not yet been reached. The Kaplan-Mier estimation of overall survival rate at 24 months was 68.7%.   Tumor viral status, as determined by small T-antigen specific antibodies in serum or large T-antigen expression in tumor biopsies by immunohistochemistry, did not correlate with any study outcomes, such as progression free survival or overall survival. However, a trend towards improvement of these outcomes appeared in patients with PD-L1-positive tumors, as defined by cell-surface PD-L1 expression on at least 1% of tumor or immune cells.   The safety profile of pembrolizumab in advanced Merkel cell carcinoma was similar to that in other studies of anti-PD-1 pathway inhibitors: 28% of patients had grade 3 or greater treatment-related adverse events, causing 14% of patients to discontinue treatment. A 73-year old male patient with widely metastatic Merkel cell carcinoma and pre-existing atrial fibrillation died after developing pericardial and pleural effusions 1 day after one infusion of pembrolizumab. Other adverse events were generally manageable and typical of complications of anti-PD-1 pathway inhibitors, including adrenal insufficiency, colitis, hyperthyroidism, hypothyroidism, infusion-related reaction, myocarditis, pancreatitis, pneumonitis, maculopapular rash and thyroiditis.   With such impressive rates of durable tumor regression and overall survival, on December 19, 2018, the FDA granted accelerated approval to pembrolizumab for treating patients with recurrent locally advanced or metastatic Merkel cell carcinoma. Today’s standard of care for advanced Merkel cell carcinoma is an anti-PD-1 pathway inhibitor, and the NCCN Clinical Practice Guidelines in Oncology in 2018 recommended avelumab, nivolumab and pembrolizumab as preferred first-line therapy for advanced Merkel cell carcinoma, ahead of cytotoxic chemotherapy.   Future studies must determine what role anti-PD-1 pathway inhibitors will play in the neo-adjuvant and adjuvant settings when managing early stage Merkel cell carcinoma with high-risk features. Prior to immune check point inhibitors, neo-adjuvant and adjuvant chemotherapy were considered case-by-case, absent strong evidence for benefit.  However, now with impressive results from anti-PD-1 pathway inhibitors in advanced Merkel cell carcinoma, adjuvant nivolumab and avelumab are being evaluated in 2 randomized phase II trials. Nivolumab is also undergoing study in the neoadjuvant setting, and researchers presented promising preliminary results of a phase I/II study at the 2018 American Society of Clinical Oncology Annual Meeting. We look to Nghiem, his colleagues and other investigators to keep us informed regarding future advances, including insights into mechanisms of resistance to the immune checkpoint inhibitors.   This concludes this JCO Podcast. Thank you for listening.

Cytotoxic T cells use Flower power In order to efficiently kill multiple target cells, cytotoxic T lymphocytes must endocytose and recycle cytotoxic granule membrane components from the immunological synapse. Chang et al. reveal that a protein called Flower facilitates granule endocytosis in a calcium-dependent manner. This biosights episode presents the paper by Chang et al. from the February 5th, 2018, issue of the Journal of Cell Biology and includes an interview with one of the paper's senior authors, Jens Rettig (Saarland University, Saarbrücken, Germany). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research. Subscribe to biosights via iTunes or RSS View biosights archive The Rockefeller University Press biosights@rockefeller.edu

Sustained autophagy contributes to the metabolic adaptation of cancer cells to hypoxic and acidic microenvironments. Since cells in such environments are resistant to conventional cytotoxic drugs, inhibition of autophagy represents a promising therapeutic strategy in clinical oncology. We previously reported that the efficacy of hydroxychloroquine (HCQ), an autophagy inhibitor under clinical investigation is strongly impaired in acidic tumor environments, due to poor uptake of the drug, a phenomenon widely associated with drug resistance towards many weak bases. In this study we identified salinomycin (SAL) as a potent inhibitor of autophagy and cytotoxic agent effective on several cancer cell lines under conditions of transient and chronic acidosis. Since SAL has been reported to specifically target cancer-stem cells (CSC), we used an established model of breast CSC and CSC derived from breast cancer patients to examine whether this specificity may be associated with autophagy inhibition. We indeed found that CSC-like cells are more sensitive to autophagy inhibition compared to cells not expressing CSC markers. We also report that the ability of SAL to inhibit mammosphere formation from CSC-like cells was dramatically enhanced in acidic conditions. We propose that the development and use of clinically suitable SAL derivatives may result in improved autophagy inhibition in cancer cells and CSC in the acidic tumor microenvironment and lead to clinical benefits. Full text - http://bit.ly/2m8L2Mk Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N www.Oncotarget.com

In Episode #24 of the Biopharma EHS podcast, Dean M. Calhoun, CIH discusses with Dr. Joe Nieusma, Senior Occupational Toxicologist for Affygility Solutions, the "Mystery of Cytotoxic Compounds." For multi-product pharmaceutical manufacturing facilities, this often a controversial topic since many people believe that cytotoxic compounds require dedicated facilities or equipment. It is also a topic of debate when setting occupational exposure limits and acceptable daily exposure values for active pharmaceutical ingredients.

The purpose of the study reported here was to compare the antiviral efficacy against feline immunodeficiency virus (FIV) and cytotoxicity in feline peripheral blood mononuclear (PBM) cells of 9 nucleoside reverse transcriptase inhibitors (NRTIs), three of which had not been evaluated against FIV in feline cells before. PBM cells were isolated from the blood of three specific pathogen-free (SPF) cats. The cytotoxic effects of the test compounds were determined by colorimetric quantification of a formazan product resulting from bioreduction of a tetrazolium reagent by viable PBM cells. Each compound was tested in 12 concentrations ranging from 0.001 to 500 M. Uninfected cells from one SPF cat were used in these assays. PBM cells (from all three SPF cats) were infected with the molecular clone FIV pPPR and the antiviral efficacy of the test compounds was assessed using a FIV p24 antigen capture enzyme-linked immunosorbent assay. Each compound was tested in 5 concentrations ranging from 0.1 to 10 M. Cytotoxic effects in feline PBM cells were observed only at concentrations over 10 M for all 9 NRTIs. Comparison of the cytotoxic effect at the highest concentration investigated (500 M) revealed that didanosine and amdoxovir were significantly less toxic than abacavir. As no cytotoxicity was noted up to a concentration of 10 M, this was set as the highest concentration for the second part of this study investigating the anti-FIV efficacy of the test compounds. All drugs induced a dose-dependent reduction of FIV replication. When compared at the highest concentration investigated, there was no significant difference in the antiviral efficacy among the test compounds. The EC50 could not be determined as none of the test compounds achieved 50% viral inhibition. The evaluated NRTIs had low cytotoxicity against feline PBM cells and appear to be safe options for further in vivo evaluation for the treatment of FIV-infected cats. There was no evidence suggesting that the newly evaluated compounds would be superior to the existing NRTIs for reducing the FIV burden of infected cats.

Thu, 25 Oct 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/14986/ https://edoc.ub.uni-muenchen.de/14986/1/Rath_Sebastian.pdf Rath, Sebastian

Introduction: The HIV protease inhibitor nelfinavir is currently under investigation as a new anti-cancer drug. Several studies have shown that nelfinavir induces cell cycle arrest, endoplasmic reticulum stress, autophagy, and apoptosis in cancer cells. In the present article, the effect of nelfinavir on human breast cancer cells is examined and potential combination treatments are investigated. Methods: The effects of nelfinavir and tamoxifen on the human breast cancer cell lines MCF7, T47 D, MDA-MB-453, and MDA-MB-435 were tested by analysing their influence on cell viability (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay), apoptosis (annexin binding, poly(ADP-ribose) polymerase cleavage), autophagy (autophagy marker light chain 3B expression), endoplasmic reticulum stress (binding protein and activating transcription factor 3 expression), and the occurrence of oxidative stress (intracellular glutathione level). Results: Nelfinavir induced apoptosis in all four breast cancer cell lines tested, although the extent of autophagy and endoplasmic reticulum stress varied among the cell lines. The concentration of nelfinavir needed for an efficient induction of apoptosis in breast cancer cells could be reduced from 15 mu g/ml to 6 mu g/ml when combined with tamoxifen. At a concentration of 6 mu g/ml, tamoxifen substantially enhanced the endoplasmic reticulum stress reaction in those cell lines that responded to nelfinavir with binding protein (BiP) upregulation (MCF7, T47D), and enhanced autophagy in cell lines that responded to nelfinavir treatment with autophagy marker light chain 3B upregulation (MDA-MB-453). Although tamoxifen has been described to be able to induce oxidative stress at concentrations similar to those applied in this study (6 mu g/ml), we observed that nelfinavir but not tamoxifen reduced the intracellular glutathione level of breast cancer cells within hours of application by up to 32%, suggesting the induction of oxidative stress was an early event and an additional cause of the apoptosis induced by nelfinavir. Conclusions: The results demonstrate that nelfinavir may be an effective drug against breast cancer and could be combined with tamoxifen to enhance its efficacy against breast cancer cells. Moreover, the cytotoxic effect of a tamoxifen and nelfinavir combination was independent of the oestrogen receptor status of the analysed breast cancer cells, suggesting a potential benefit of a combination of these two drugs even in patients with no hormone-responsive tumours. We therefore recommend that clinical studies on nelfinavir with breast cancer patients should include this drug combination to analyse the therapeutic efficacy as well as the safety and tolerability of this potential treatment option.

Background: Nelfinavir is an HIV protease inhibitor that has been used for a long period of time to treat HIVinfected individuals. It has recently emerged that nelfinavir could represent a prospective new anti-cancer drug, prompting us to test the effect of nelfinavir on leukemia cells. Methods: By combining in vitro and ex vivo studies, the effect of nelfinavir on leukemia cells and non-malignant, bone marrow-derived tissue cells was analyzed. Results: At a concentration of 9 mu g/ml, nelfinavir induced death of 90% of HL60, IM9, and Jurkat cells. At the same concentration and treatment conditions, less than 10% of aspirated human bone marrow cells showed nelfinavir-induced cell damage. Nelfinavir-induced death of leukemia cells was accompanied by activation of caspases 3, 7, and 8. Despite caspase activation, the upregulation of the anti-apoptotic bcl-2 family member protein mcl-1 that resulted from nelfinavir treatment stabilized the mitochondrial membrane potential, resulting in primarily mitochondria-independent cell death. Pharmacological downregulation of mcl-1 expression by treatment with sorafenib (2 mu g/ml) significantly enhanced nelfinavir-induced apoptosis even at lower nelfinavir concentrations (5 mu g/ml), but did not have additional detrimental effects on non-malignant bone marrow cells. Conclusions: The ability of nelfinavir to induce apoptosis in leukemia cells as a single agent in a mitochondria-independent manner might suggest it could be used as a second or third line of treatment for leukemia patients for whom standard mitochondria-directed treatment strategies have failed. Combination treatment with nelfinavir and sorafenib might further enhance the efficacy of nelfinavir even on chemo-resistant leukemia cells.

Part I: Cephalostatin 1 is a potent marine cytotoxic compound reported to induce apoptosis without cytochrome c release and apoptosome formation. This work shows that, however, caspase-9 is essential for the induction of apoptosis. Cephalostatin 1 induces endoplasmic reticulum stress together with the activation of the ASK1/JNK cascade as well as caspase-4 and caspase-2, which act upstream of caspase-9 and are required for apoptosis. Part II: Sesquiterpene lactones are secondary plant metabolites with cytotoxic and anti-inflammatory activities. It was found that 11α,13-dihydrohelenalin acetate (α,β-unsaturated cyclopentenone) induces classical apoptosis whereas 7-hydroxycostunolide (α-methylene-γ-lactone) induces a novel form of cell death characterised by a fast and strong exposure of phosphatidylserine in agreement with a strong activation of phagocytosis in cocultured macrophages.

Bakterielle Toxine aktivieren spezifische Signalwege in humanen Zellen und modulieren so deren Funktion und Morpholgie. Ein besseres Verständnis der Effekte von Toxinen auf humane Zellen könnte zur Aufklärung der Pathogenese bakterieller Erkrankungen beitragen. In dieser Arbeit wurde der Effekt des Exotoxins CNF-1 aus Escherichia coli auf die Morphologie humaner Endothelzellen (HUVEC) und die beteiligten Signalwege untersucht. CNF-1 führt in HUVEC zeitabhängig sowohl zur Bildung von Aktinfasern als auch zur Ausbildung von "membrane ruffles" und Filopodien. Diese Aktinstrukturen werden durch Aktivierung der GTPasen Rho, Rac und CDC42 induziert. Rho führt in Endothelzellen über Rho-Kinase zu einer Myosinleichtketten (MLC)- Phosphorylierung und dadurch zur Hemmung von MLC-Phosphatase. Stimulation der Endothelzellen mit CNF-1 führt hingegen abhängig von Rho und Rho-Kinase ohne Hemmung der MLC-Phosphataseaktivität zu einem Anstieg der MLC-Phosphorylierung und einer Zellkontraktion. Es konnte gezeigt werden, dass zwar Rac und CDC42 in den ersten Stunden durch CNF aktiviert werden, diese aber nicht für die MLC-Phosphorylierung verantwortlich sind. 24h nach CNF-Stimulation zeigt sich immer noch eine Aktivierung von RhoA, nicht aber von CDC42 und Rac. Trotzdem kommt es zu einem Anstieg der MLC-Phosphatase und dadurch zu einem Abfall der MLC-Phosphorylierung und Zellausbreitung. Diese Ergebnisse zeigen, dass CNF zu einer Entkopplung des Rho, Rho-Kinase, Myosinleichtketten-Phosphatase-Signalweges führt. Diese Entkopplung könnte eine Rolle bei der pathologischen Wirkung des Toxins spielen.

The nature of alloreactivity to MHC molecules has been enigmatic, primarily because of the observation that allogeneic responses are considerably stronger than syngeneic responses. To better determine the specificity potential of allogeneic responses, we have generated alloreactive CTL specific for exogenous, viral-derived peptide ligands. This approach allowed us to critically evaluate both the peptide- and MHC-specificity of these alloreactive T cells. Exploiting the accessibility of the H-2Ld class I molecule for exogenous peptide ligands, alloreactive CTL were generated that are specific for either murine cytomegalovirus (MCMV) or lymphocytic choriomeningitis virus (LCMV) peptides bound by Ld alloantigens. Peptide specificity was initially observed in bulk cultures of alloreactive CTL only when tested on peptide-sensitized T2.Ld target cells that have defective presentation of endogenous peptides. Subsequent cloning of bulk alloreactive CTL lines generated to MCMV yielded CTL clones that had exquisitely specific MCMV peptide recognition requirement. All of the MCMV/Ld alloreactive CTL clones were also exquisitely MHC-specific in that none of the CTL clones lysed targets expressing MCMV/Lq complexes, even though Lq differs from Ld by only six amino acid residues and Lq also binds the MCMV peptide. This observation clearly demonstrates that alloreactive CTL are capable of the same degree of specificity for target cell recognition as are syngeneic CTL in MHC-restricted responses.

Tue, 1 Jan 1991 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6728/1/Koszinowski_Ulrich_6728.pdf Forman, J.; Stroynowski, I.; Hood, Leroy; Koszinowski, Ulrich H.; Jones-Youngblood, S.; Hammer, R. E.; Aldrich, C. J.

Cytotoxic T cell responses to the murine Cytomegalovirus (MCMV) were elicited in BALB/c mice (H-2d) by infectious virus. Eight days after infection, MCMV-primed local lymph node T cells were either depleted for T cells expressing a V beta 8+ TCR or separated into V beta 8+ and V beta 8- subpopulations by a cell sorter using the mAb F23.1. T cells were then expanded in vitro under limiting dilution conditions in the presence of IL-2 and in the absence of viral Ag to avoid selection by Ag in vitro. Frequencies of CTL precursors specific for the Immediate- Early-Ag 1 of MCMV and restricted to H-2Ld were determined. L cells of the endogenous haplotype H-2k cotransfected with the genes for MCMV-IE 1 and H-2Ld were used as target cells. Detection of a CTL response required previous priming of the animals by infection in vivo (less than 1/10(6) for nonimmunized animals). In primed animals CTL precursors of this specificity and restriction were three to fivefold more frequent in the V beta 8+ population (1/9.900 to 1/22.300) than in the V beta 8- population (1/57.000 to 1/87.200). Control experiments showed that frequencies were not influenced by the treatment with the anti-V beta 8-antibody and the fluorescein-labeled anti-Ig itself. V beta 8+ and V beta 8- T cells did not reveal any frequency differences when several other responses were determined (TNP-specific self- restricted CTL precursor; Th cells specific for keyhole limpet hemocyanin or Listeria monocytogenes).

Using noninfectious Sendai virus preparations after selective enzymatic digestion of either of the two viral envelope glycoproteins, it was possible to study the effect of different virion-cell membrane interactions on virus-specific cytotoxic T lymphocyte (CTL) induction in vitro. Three different virus preparations having capacity for virus- cell fusion, for virus-cell adsorption or lacking the ability to bind to cell membranes, were all active in the generation of virus-specific primary and secondary cytotoxic T cells, when added to the culture. Investigations on the responder cell requirements during CTL induction revealed that activation by addition of virions lacking the capacity to bind to cells was sensitive to the depletion of adherent cells. When virions with fusion and binding capacity were presented on tumor stimulator cells, different requirements with respect to adherent cells were obtained in the primary and secondary CTL response to Sendai virus. The data indicate that different viral antigen-cell membrane interactions govern the activation phase and effector phase of antigen- primed T cell populations, while sensitization of unprimed cells is dependent on the presence of adherent, perhaps antigen-presenting cells.

H-2-restricted cytotoxic T cells specific for Sendai virus were generated in vitro in a primary response from normal mouse lymphocytes cultured in the presence of infective as well as inactivated Sendai virus. Antigen-presenting cells of different origin, including T cells, were found to be effective stimulators. Antibodies to Sendai virus were shown to inhibit the activation of specific precursor killer cells when added to cultures before, but not after, the addition of viral antigen. Data obtained by Lyt phenotyping, revealed that precursor killer cells specific for Sendai virus reside in the Lyt-2,3+ T cell population and that Lyt-l,2,3+ T cells are not required for the generation of cytotoxic lymphocytes. Different activation kinetics were demonstrated for primary and secondary antiviral cytotoxic responses, and the analysis of the proliferation and stimulation requirements suggests qualitative differences.

Mon, 1 Jan 1979 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6769/1/6769.pdf Neuschaefer-Rube, I.; Greber, D.; Koszinowski, Ulrich H. ddc:610, Medizin

Sat, 1 Jan 1977 12:00:00 +0100 https://epub.ub.uni-muenchen.de/6960/1/6960.pdf Ertl, Hildegund; Koszinowski, Ulrich H.

Vaccinia virus specific cytotoxicity against infected target cells was observed in vitro. Spleen lymphocytes from normal and immunized mice of the inbred strains C3H and DBA/2 were incubated with vaccinia virus-infected and non-infected 51Cr-labeled mastocytoma P-815-X2 cells and L-929 fibroblasts, which were used as targets. Cytotoxic lymphocytes could be isolated from the mice as early as 2 days after infection with vaccinia virus. The highest cytotoxic effect was obtained with lymphocytes taken 6 days after infection. The degree of lysi was correlated with the ratio of immune lymphocytes to target cells. Specific blocking of target cell lysis resulted after addition of anti-vaccinia antibody from different sources. The effector cells could be characterized as T cells by elimination of macrophages and B cells. Target cell killing was only possible in a syngeneic system; allogeneic infected target cells were not lysed significantly.